We monitored [Na^+]i and [Ca^<2+>]i simultaneously using SBFI/AM and fluo-3/AM in guinea pig ventricular myocytes. After the addition of 500 muM strophanthidin, [Na^+]i increased from 7.9(〕SY.+-.〔)0.4 mM (mean(〕SY.+-.〔)SE) to 19.6(〕SY.+-.〔)1.8 mM at 40 min. [Ca^<2+>]i was low during the first 20 min, and then began to increase to 361(〕SY.+-.〔)69 % of the control at 40 min. The addition of hexamethylene amiloride (HMA : 1muM) prevented the increases in both [Na^+]i and [Ca^<2+>]i. Ryanodine (1muM) suppressed the increase in [Ca^<2+>]i. These findings indicated that (1) the pathway of Na^+ entry was mainly through Na^+/H^+ exchange, and that the elevated [Na^+]i induced Ca^<2+> entry mediated by the Na+/Ca^<2+> exchange, (2) the entered Ca^<2+> triggered the Ca^<2+> release from the sarcoplasmic reticulum. For metabolic inhibition (MI), the perfusate contained 3.3 mM amytal and 5 muM CCCP.During the first 20 min of MI, [Na^+]i increased from 6.2(〕SY.+-.〔)0.5 mM to 18.6(〕SY.+-.〔)1.6 mM (p<0.01, m=31), whereas [Ca^<2+>]i remained at the low level. In the following 30 min, 29 of 31 (94 %) myocytes developed contracture, and [Ca^<2+>]i began to increase after cells had contracted until it reached to 167(〕SY.+-.〔)14 % of the control (p<0.01). The levels of [Ca^<2+>]i when cells contracted or hypercontracted during MI were much lower than those during 500 muM strophanthidin perfusion, whereas [Na^+]i increased further. It was shown that there was a dissociation in the relationship between [Na^+]i and [Ca^<2+>]i during MI.The increase in [Na^+]i during MI was suppressed by 1 muM HMA or 10 mM glucose. The addition of 10 mM glucose after 20 min of MI led to a dramatic increase in [Ca^<2+>]i to 442(〕SY.+-.〔)72 % of the control (50 min. n=31, p<0.01). The increase in [Ca^<2+>]i and cell contracture after energy repletion were suppres